SEARCH

SEARCH BY CITATION

Keywords:

  • halogen bonding;
  • medicinal chemistry;
  • molecular recognition;
  • protein–ligand interactions;
  • structure–activity relationships
Thumbnail image of graphical abstract

Halogen bonding triggers activity: Increasing binding affinity was observed for a series of covalent human Cathepsin L inhibitors by exchanging an aryl ring H atom with Cl, Br, and I, which undergo halogen bonding with the C[DOUBLE BOND]O group of Gly61 in the S3 pocket of the enzyme. Fluorine, in contrast, strongly avoids halogen bonding (see scheme). The strong distance and angle dependence of halogen bonding was confirmed for biological systems.